A jaundiced 35 year old with late quadriparesis


MRI T2/FLAIR on day 17

A 36 year old alcoholic man was admitted to hospital with obtunding, jaundice and cachexia. In addition to deranged LFTs, anaemia and thrombocytopenia, all thought to be related to cirrhosis, he had Creat 194 (eGFR 36), Na 138, K 2.6. He was treated for alcohol withdrawal but was difficult to manage; for a few days he was intubated and ventilated. Lactulose was thought to blame for very profuse diarrhoea, and he developed significant electrolyte disturbance. Serum sodium rose to 158 over 30 hours at one point; then slowly improved with water hydration over several days. Potassium rose to 3.4 then dropped back to 2.4 before slowly returning to normal.

5 days later his conscious level reduced again and he developed spastic quadriplegia. An MRI scan later that day is shown above.

Question: what is the likely caused of this problem? Could anything have been done to prevent it?

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What the experts thought ...

This is osmotic demyelination (old name: Central Pontine Myelinolysis) but it is a very unusual example caused by rapid onset of hypernatraemia. Usually it is attributed to too-rapid correction of very low plasma [Na], but presumably the principle is the same. A few principles.

  • The hyponatraemia needs to be of some duration (not acute).
  • The delayed onset of symptoms, 2-6d after the peak change in sodium, is typical.
  • A ‘safe rate’ for correction of chronic hyponatraemia is said to be less than 8 mmol every 24h (up to 10 mmol quickly for severe acute symptoms). (UpToDate)(UoE login required).
  • Risk factors for its occurrence include alcohol abuse, liver disease, malnutrition, pre-existing brain disease. It is also much more likely if starting sodium is <120.

What happened? He is said to have made a good neurological recovery over a week or so. This is not always the case.

Further info

This case is adapted from Am J Kid Dis 68(5):xv-xvii (2016). The image is courtesy of Dr Lemuel Marquez Narcise, Radiopaedia.org, from the case rID: 44204

A breathless 20 year old with cough and fever

A 20 year old man complains of 3 weeks of cough and fever, and 4 days of oedema of his feet. On examination he is breathless.  There is marked engorgement of his neck veins, JVP higher than ears, ascites, 2+ oedema of his feet. P130/min irregularly irregular, of waxing and waning volume, apex rate 160. BP 95/80. Liver 4cm. There was dullness and reduced breath sounds at R lung base. His chest radiograph is shown.

ECG showed inverted T waves across anterolateral chest leads.

Questions

What is the likely diagnosis. What complication sounds imminent, and what would you do about it. What is the most likely cause?

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Show what happened next

He has a pericardial effusion with tamponade. 500 mls of bloody fluid were drained from the pericardium, with immediate improvement in breathlessness and blood pressure. 1000 ml of similar fluid was drained from the right pleural cavity. Microscopy did not show a cause.

The effusion recurred a week later, so a pericardial biopsy was undertaken. Don’t try this at home.

A week later the problem recurred. A biopsy was undertaken.

What might it show?

Show the outcome

The fluid again did not give a diagnosis, but the pericardial biopsy showed giant cell granulomas. A guinea pig was inoculated with the fluid, and 5 weeks later it had developed tuberculous lesions, confirming the diagnosis.

TB is a rare cause in UK practice. Viral causes are probably the most common cause of symptomatic acute pericarditis, followed by autoimmunity. However big effusions causing tamponade are probably most likely after cardiac surgery or myocardial injury (Dressler Syndrome), and in malignancy. Infections are a less common cause.

Further info

This case is from Sanghvi et al 1958, Sawai Man Singh Hospital and Medical College Rajasthan (Pericardial biopsy with Vim-Silverman needle, Archives of Internal Medicine 101:1147-10). Pushing a big biopsy needle towards the heart sounds hazardous, and probably fortunately the approach didn’t catch on. Guinea pig inoculation was a quicker, less demanding technique than TB cultures, though these had been developed in the 1930s.

Pericarditis from TB is rarely encountered in developed countries now, but still not rare worldwide. Drug resistance, and co-infection with HIV, are important issues. Surgery may be required in chronic examples, but is not always available in the areas of highest incidence.

Further further info

History of tuberculosis (Wikipedia) and Timeline of tuberculosis (Wikipedia) are both fascinating.

The image shows a modified Vim Silverman needle, the predecessor of the ‘Trucut’ cutting needle developed for liver biopsies, extended in the mid 1950s to renal biopsies (Renal biopsy becomes mainstream, 1954).

A patient with big kidneys

A 48 year old man is found to have BP 170/95 and a follow-up blood test shows eGFR 55.  The abdomen seems to contain hard masses.  On following this up, this investigation is undertaken:

PKD liver and kidney MRI radiopaedia 5202

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After the quiz, a couple more questions

So that’s the diagnosis.  What is the prognosis likely to be?  Is there anything you can do to alter it?

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Show what the experts thought?

This is advanced PKD with very large kidneys and not much normal kidney tissue in between the cysts. This patient is likely to be heading for dialysis and/or a renal transplant. It is amazing that liver failure is extremely rare in PKD, despite sometimes massive cyst formation – though there can be physical symptoms from all this extra volume in the abdomen.

PKD accounts for close to 10% of end stage renal disease in most countries.

Management of PKD has been mostly symptomatic until recently, but the first drug to slow down the progressive growth of cysts is now licensed: Tolvaptan, an ADH receptor antagonist.  CKD issues in PKD are the same as for any other patient with renal impairment.

Further info

The image shown is courtesy of Prof Frank Gaillard (Radiopaedia)

A girl with facial swelling

[pic from Thyolo] A 14 yearl old schoolgirl is referred from Thyolo District Hospital, Malawi, complaining of facial swelling for 3 weeks, worse in the morning.  3 days later she developed bilateral leg swelling and increasing abdominal distension with some suprapubic colicky pains.  She reported concentrated urine but no haematuria.  There was no significant past medical history but 1-2 weeks previous to her symptoms she was treated for malaria when she had a fever.  Anaemia was noted at that time and she was given Albendazole and ferrous sulphate.  A week before admission she was treated for vaginal discharge with Gentamicin 240mg IM one dose, and a course of Doxycycline and Metronidazole.  She had also taken some herbal medicines for her symptoms.

She now complains of feeling ill, anorexia, and is vomiting once or twice a day.

Her father works on a tea estate as a labourer.  The family can afford 3 meals a day.

On examination she was unwell but not distressed, appeared well nourished.  Temperature 36.5C, pulse 96, BP 168/94, respiratory rate 16.  She had pale conjunctivae and facial oedema that she said was improved.  Pedal oedema had also mostly resolved.  There were no skin lesions or rash.  Throat was normal and she had no lymphadenopathy.  Her JVP was not elevated. Heart sounds were normal.  There was evidence of some ascites but again this seemed to be improved.

Urine dipstick showed blood 3+, protein 3+, and was negative for leucocytes and nitrite

Before showing results, what syndrome does she have?  What do you think the diagnosis is likely to be?

Case contributed by Emmanuel Mwabutwa

Show test results

  • HIV test negative
  • Pregnancy test negative
  • Hb 5.3 (MCV 70), wbc 4.3, plats 170
  • Creatinine was 19.3 mg/dl (1700 micromol/l) 3 days ago, having risen from 15.3 mg/dl (1350 micromol/l) 4 days previously.
  • Ultrasound showed kidneys to be normal in size but bright in echo pattern.  It confirmed ascites.  A cardiac echo showed a 1.6cm pericardial effusion but normal ejection fraction (76%) and appearances. The right atrium and hepatic veins were dilated.

Now write what you think and what you'd do

Show what the experts thought?

She has acute nephritic syndrome – fluid retention, hypertension (BP very high for a 14 year old) and renal impairment with strongly positive dipstick tests for haematuria and proteinuria.  These confirm glomerular disease.

The most likely diagnosis is classic post-infectious glomerulonephritis.  The normal kidney size and lack of left ventricular hypertrophy support an acute condition, rather than an exacerbation of something chronic.

She also has severe anaemia with microcytosis suggesting iron-deficiency.  Anaemia is frequent in the population and can be multifactorial related to malaria, diet, or other factors.

Her renal impairment is severe and life-threatening.  We do not have a potassium result.  Usually post-infectious glomerulonephritis in children resolves spontaneously, and there are probably many sub-clinical cases. At its most severe, dialysis may be required, but good recovery is still usual.  Even severe cases can usually be managed conservatively:

  • Diet:  Limit salt intake (about zero is right if they are oedematous and hypertensive); limit potassium intake
  • Restrict protein intake but provide plenty of calories.  Oedema can hide severe wasting
  • Loop diuretics relieve fluid retention in all but the most severe cases, and improvement in fluid balance improves blood pressure, though additional measures may be required.

Further info

A 44 year old man with previous interstitial nephritis (22)

This man was diagnosed with interstitial nephritis secondary to mesalazine (prescribed for ulcerative colitis) in 2009.  His eGFR has remained stable since and is curently 42.  Last year he was started on lisinopril for hypertension but this was stopped some months later as his BP was too low.  The plan then was to reintroduce if BP over 130/80 or if proteinuria worsened.  Urinary PCR was 15 mg/mmol.

His PCR has increased a bit to 20; blood pressure on his last two visits 123/83, 124/96.  I just wanted to check that we should add in lisinopril 2.5mg in vew of this.

I also note that his cholesterol was recently 6.1, LDL 4.2, chol/HDL ratio 4.2.  I wonder if we should be starting a statin also?  He has no significant family history of heart disease and is an ex-smoker.  Other therapy is azathioprine (only) for ulcerative colitis.

Write what you think and what you'd do

Show the answer?

That level of proteinuria, just outside the normal range, wouldn’t trigger me in his case.  Any threshold is going to be arbitrary, but 50 is sometimes uesd.  Consistently over 50 maybe.  His BP is well within limits. His CV risk is low (see Further Info)

Proteinuria is in general a strong marker for progression of renal disease, with higher levels indicating much higher risk.  Mostly we are talking about glomerular leaking of protein.  He actually had tubulointerstitial disease rather than glomerular, which is associated iwth lower levels of proteinuria in general, and lower risk of progression if the cause is removed (as it is in him).

If he showed any signs of long term deterioration I’d be stricter but he seems to have experience a small fall in creatinine over the last couple of years.

Further info

  • CV risk calculator gives him a 10y risk of CV events of 3.6% – this does not include proteinuria however, which would ‘usually’ probably at least double risk, though this is contentious in this patient’s unusual circumstances.
  • Interstitial nephritis (Edren Textbook)
  • The Edrep Glomerulonephritis page has a link to a 10 min lecture on Interstitial nephritis (requires Flash).  The Resources page there has more links

A 4 year old boy with patchy hair loss

A healthy 4 year old boy is brought to the Dermatology clinic at Queen Elizabeth Central Hospital, Blantyre by his parents.  He has been scratching his head, and they have recently noticed that he has developed several small scaly areas with associated hair loss.

What is your diagnosis and how would you treat him?

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The diagnosis is tinea capitis (scalp “ringworm”).  This is a cutaneous fungal infection which invades the hair shaft and is often due to Trichophyton tonsurans (caught from other children) or Microsporum canis (caught from kittens or puppies). Without treatment it gets better spontaneously at puberty.  After puberty it only occurs in patients with underlying immunosuppression.

Treatment of choice is oral griseofulvin 15-20mg/kg/day for 6 weeks.  Additional application of a topical antifungal, during the early stages of treatment, may reduce the risk of transmission.  Terbinafine is an unlicensed alternative, but may not be as effective for infections with M. canis.   The only oral antifungal available in the department is ketoconazole, so he is prescribed this and topical Whitfield’s ointment.  His parents then tell you that his elder sister was treated with the same treatment successfully earlier this year.

Other siblings with infection should also be treated and if the family pet’s fur is falling out it must be treated too.

The other differential diagnosis to consider in this case is alopecia areata but the presence of scale distinguishes these diagnoses.

Further info

 

This case contributed by Levie Mwale and Ann Sergeant

 

A 34 year-old man with a fit

A 34 year old man presents to Queen Elizabeth Central Hospital, Blantyre with a 2 day history of frontal headaches and generalized tonic clonic seizures. His guardians report that he has had multiple nodules all over his body since childhood but has previously been well.

He has another prolonged seizure after admission. He is post-ictal on examination with a Glasgow Coma Scale 11/15 (E -4, V-2, M-5). His pupils are of normal size and equally reacting to light. His vital signs on admission are: blood pressure 121/81mmHg, pulse 94/min, temperature  37.0°C, respiratory rate 24/min. The chest and abdominal examination are normal. The rest of the neurological exam does not reveal  any focal deficits.

  1. What is his underlying condition?
  2. What differential diagnoses are you considering?
  3. What tests would you want to do?
  4. What would your initial management be?

Write what you think and what you'd do

Show the answer?

The recent history of headaches raises the possibility that this is more than simple epilepsy, though his underlying condition is associated with epilepsy.  This is a region where there is a high prevalence of HIV infection, the possibility of which broadens the differential diagnosis importantly.

His underlying condition is  neurofibromatosis type 1.  It is associated with epilepsy and with astrocytomas, gliomas, but at presentation it may be causative or just a coincidence.  

Tests you should seek:

  • Blood glucose
  • Full blood count
  • Malaria blood film
  • Lumbar puncture with examination to include India Ink stain (if available you would test for Cryptococcal antigen)
  • HIV test
  • Urea and electrolytes
  • Brain imaging (but CT /MRI not available here)
  • Serology for syphilis

Differential diagnosis

  • Epilepsy – simple or caused by neurofibromatosis-associated brain lesions
  • Cerebral malaria is more likely in children than adults
  • Metabolic – DEFG; Don’t ever forget Glucose.  Hypoglycaemia may induce coma and convulsions.  Other metabolic disturbances including hyponatraemia
  • Meningitis – particularly TB or Cryptococcal meningitis in the presence of HIV infection
  • Infective focal brain lesions:  Toxoplasmosis, primary CNS lymphoma – usually HIV-related; Cysticercosis, neurosyphilis

Initial management

  • Control continuing convulsions with diazepam IV.

Then in this setting:

  • Phenobarbitone 600mg loading dose (infusion or slow push) the 90mg maintenance (IM or orally if patient can tolerate it) OR Phenytoin 900mg loading dose (infusion) then 100mg tds maintenance.  Blood monitoring is not available.
  • Empirical cover for meningitis until CSF results back: Ceftriaxone 2g bd IV

For options in other centres, see …

This case contributed by Dr Tamara Phiri

 

A 16 year old girl with oedema

A 16 year old girl presents to Queen Elizabeth Hospital, Blantyre with a two-month history of facial oedema.  It is worse in the morning, slightly better at night and not associated with shortness of breath or cough.  She has been well recently, with no intercurrent illnesses. Some kind of antimicrobial was prescribed a month ago, but the swelling was present then and has increased since.

On examination she is slim but has marked bilateral pitting pedal oedema and facial puffiness; her abdomen is also distended, with shifting dullness.  She is apyrexial.  General examination is unremarkable.  Her BP is 112/65, pulse 72.  She has reduced breath sounds and dullness to percussion at both lung bases.  Heart sounds and abdomen are normal and she has no neurological deficit.

A urine dipstick shows 4+ protein.  She has a serum creatinine of 60 micromol/l (0.7 mg/dl) and a normal blood count.  Tests of liver function, serum proteins are not available.

  1. What is the differential diagnosis?
  2. Renal biopsy is not immediately available here.  What management will you recommend?  How will you advise her and her parents?

Write what you think and what you'd do

Show the answer?

With 4+ proteinuria and oedema there can be little doubt that she has nephrotic syndrome.  It is ‘pure’ nephrotic syndrome, meaning heavy proteinuria without any haematuria, which puts it at the extreme left hand end of the spectrum (see Glomerulonephritis) and makes it significantly less likely that it is caused by post-streptococcal glomerulonephritis or other disorder more toward the ‘nephritic’ end of the spectrum.

She should severely restrict salt intake: oedema is caused by salt retention.  Diuretics are often required, usually loop diuretics.

HIV is an important condition in this region.  An HIV test is important both because the condition could be a manifestion of HIV affecting the kidney, and because most active treatments for nephrotic syndrome involve immunosuppressive agents.

Minimal change disease would be the most likely explanation in a Caucasian girl.  However FSGS is more common as a cause of nephrotic syndrome in Africans: one of these two conditions is most likely. SLE is very unusual before menarche.

If she is HIV negative, a trial of prednisolone, 1mg/kg/day for a few weeks would be worthwhile.

Further info

This case is was contributed by Fran Th’ng and Gavin Dreyer

A 25 year old woman with a rash and raised creatinine

A 25 year old woman is referred with a 6 month history of fatigue, joint pain, pleuritic chest pain and facial rash. Three months ago at another hospital she was found to be unwell with a Creatinine of 500 micromol/l, Hb 8.2 g/dl, and urinalysis showed 3+ protein, 3+ blood. She was treated with some tablets (identity unknown) and a subsequent creatinine was 200 and Hb rose to 12 g/dl. Now she is unwell again.

On examination she has a rash around her nose and on her cheeks. She is febrile, 38.2C, and has mild swelling of her left and right MCPJ. She is slim and does not look Cushingoid. BP 155/87. There is no oedema and examination of chest, cardiovascular system and abdomen are normal. She has a platelet count of 50 and Hb 6.2g/dl, Creatinine 430 micromol/l, and urinalysis continues to show 3+ for both protein and blood.

Three questions:

  1. What is the likely underlying diagnosis?
  2. What other urgent (not too complicated) test results are important?
  3. How would you treat the underlying disease given that a renal  biopsy is not possible?

Thanks to Dr Gavin Dreyer for this case.

Write what you think and what you'd do

Show the answer?

Diagnosis:  Lupus seems the most likely underlying diagnosis.

Tests (1) She had a high level of Malaria falciparum parasitaemia. (2) She was HIV non-reactive.
Neither infection would do well with immunosuppressive therapy for lupus. The level of HIV positivity in the region is high, but in sick patients, in particular medical inpatients, it is much higher (up to 80%).
Ideal initial treatment according to WHO should be Artemisinin combination therapy, but it is not generally affordable so Quinine is still most commonly used. She responded to treatment and her Hb rose.

Treatment beyond this point is difficult, but almost certainly she has aggressive inflammatory disease in view of the creatinine changes, and will need cyclophosphamide. Some might argue for MMF in a young woman, but it is less well tested, and much more expensive.

Other diagnostic possibilities?
Classic HIV nephropathy usually has a more extreme nephrotic phase. Of course many other renal pathologies can occur in HIV infection.

Further info

An HIV positive woman with low eGFR

A 38 year old woman who has been on anti-retroviral therapy for 3 years is found to have a creatinine of 230 micromol/l (2.6 mg/dl).  She is taking Tenofivir, Efavirenz and cotrimoxazole and has been compliant with therapy.  She complains of recurrent dysuria and frequency, as well as intermittent fevers which do not always seem related to urinary symptoms.  She describes some vaginal discharge.

On examination she is thin but not emaciated.  She has no oedema.  Her pulse is 64, blood pressure 110/60, chest is clear, cardiovascular system normal.  She has mild non-specific abdominal tenderness but no masses.

Urine dipstick is positive for nitrites and leucocytes, blood 1+.

What type of disease process do you suspect?  What further features or investigations would you immediately seek?

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Show the answer?

She has marked renal impairment; that creatinine corresponds to an eGFR of about 26.  She already has possible explanations for renal disease from her diagnosis of HIV and the fact that she is on anti-HIV drugs, many of which have renal side effects, including crystallization, interstitial nephritis, tubular injury.

A key observation is the bland urinary sediment, showing little protein or blood, which essentially rules out severe glomerular pathology.  HIV nephropathy is a glomerulopathy, so it is an unlikely explanation. Using the pre-renal/renal/post-renal algorithm, this makes you home in on

  • Pre-renal causes.  She doesn’t sound very dehydrated, but pre-renal causes include arterial and small vessel disease; for instance thrombotic microangiopathy can occur in HIV.
  • Interstitial or tubular causes (drugs particularly likely to be implicated; tenofivir is associated with tubular injury)
  • Obstruction

The key investigation in any patient with renal failure and urinary symptoms is renal imaging.  Ultrasound is quick, non-invasive, risk-free, and almost always first choice; it should be part of the investigation of almost any patient with unexplained new severe CKD.  It showed bilateral hydroureter and hydronephrosis without distention of the bladder.

Hope you had also written that vaginal examination is one of the things that you must do here.  She had advanced cervical cancer involving both ureters.

She also had a CD4 count of 93 despite her anti-HIV therapy, with PCR showing 5,000 copies per ml, suggesting anti-retroviral failure.  In a well-resourced setting you would consider testing for drug resistance.

Further info

Thanks to Fran Th’ng and Gavin Dreyer for this case.